Näveri L
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Acta Physiol Scand Suppl. 1995;630:1-48.
The present studies were conducted to examine the roles of angiotensin II, angiotensin IV, and the angiotensin receptor subtypes in the cerebral circulation. The effects of angiotensin II, the selective AT1 receptor antagonist losartan, and the selective AT2 receptor ligands, PD 123319 and CGP 42112, on cerebral blood flow autoregulation, were studied during increases and decreases in blood pressure in normotensive rats. Cerebrocortical blood flow was measured by laser-Doppler flowmetry, while systemic blood pressure was either increased by phenylephrine infusion, or decreased by controlled haemorrhage. The effects of angiotensin II, and AT1 and AT2 receptor ligands on the contractility of rat anterior cerebral artery in vitro, were studied using cannulated, perfused vessel segments. The effect of angiotensin IV on cerebral blood flow after experimental subarachnoid haemorrhage, and possible involvement of nitric oxide, was studied in rat. Subarachnoid haemorrhage was simulated by injecting 0.3 ml arterial blood into the cisterna magna, while cerebral blood flow was measured by laser-Doppler flowmetry. The main findings in the present studies were that angiotensin II, the AT1 antagonist losartan, and the AT2 ligands PD 123319 and CGP 42112, shifted the cerebral blood flow autoregulatory range towards higher blood pressures. PD 123319 and CGP 42112 acted as AT2 receptor agonists. In vitro, angiotensin II elicited an AT1 receptor mediated contraction of rat anterior cerebral artery. Angiotensin IV was able to reverse the acute CBF reduction after subarachnoid haemorrhage. No evidence was found to support the involvement of nitric oxide in this response. In conclusion, there is strong evidence supporting a role for the AT2 receptor in the regulation of cerebral circulation. The role of the AT1 receptor is questionable, and the losartan induced autoregulatory shift is possibly mediated indirectly through AT2 receptor stimulation. Although AT1 receptors mediate the angiotensin II induced contraction of rat anterior cerebral artery in vitro, this effect does not explain the effect of losartan on CBF autoregulation. Angiotensin IV increases cerebral blood flow after experimental subarachnoid haemorrhage possibly by dilating cerebral vessels through stimulation of the AT4 receptor.
本研究旨在探讨血管紧张素II、血管紧张素IV及血管紧张素受体亚型在脑循环中的作用。在正常血压大鼠血压升高和降低期间，研究了血管紧张素II、选择性AT1受体拮抗剂氯沙坦以及选择性AT2受体配体PD 123319和CGP 42112对脑血流自动调节的影响。通过激光多普勒血流仪测量大脑皮质血流量，同时通过注入去氧肾上腺素升高或通过控制性出血降低全身血压。使用插管灌注的血管段研究血管紧张素II以及AT1和AT2受体配体对大鼠大脑前动脉体外收缩性的影响。在大鼠中研究了血管紧张素IV对实验性蛛网膜下腔出血后脑血流的影响以及一氧化氮可能的参与情况。通过向小脑延髓池注入0.3 ml动脉血模拟蛛网膜下腔出血，同时通过激光多普勒血流仪测量脑血流量。本研究的主要发现是，血管紧张素II、AT1拮抗剂氯沙坦以及AT2配体PD 123319和CGP 42112使脑血流自动调节范围向更高血压偏移。PD 123319和CGP 42112作为AT2受体激动剂起作用。在体外，血管紧张素II引起大鼠大脑前动脉由AT1受体介导的收缩。血管紧张素IV能够逆转蛛网膜下腔出血后急性脑血流量的减少。未发现支持一氧化氮参与此反应的证据。总之，有强有力的证据支持AT2受体在脑循环调节中起作用。AT1受体的作用存在疑问，氯沙坦诱导的自动调节偏移可能是通过刺激AT2受体间接介导的。尽管AT1受体在体外介导血管紧张素II诱导的大鼠大脑前动脉收缩，但这种作用并不能解释氯沙坦对脑血流自动调节的影响。血管紧张素IV在实验性蛛网膜下腔出血后可能通过刺激AT4受体扩张脑血管来增加脑血流量。
